Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial

被引:1846
作者
Gerstein, Hertzel C. [1 ,2 ]
Colhoun, Helen M. [3 ]
Dagenais, Gilles R. [4 ]
Diaz, Rafael [5 ]
Lakshmanan, Mark [6 ]
Pais, Prem [7 ]
Probstfield, Jeffrey [8 ]
Riesmeyer, Jeffrey S. [6 ]
Riddle, Matthew C. [9 ]
Ryden, Lars [10 ]
Xavier, Denis [7 ]
Atisso, Charles Messan [6 ]
Dyal, Leanne [1 ,2 ]
Hall, Stephanie [1 ,2 ]
Rao-Melacini, Purnima [1 ,2 ]
Wong, Gloria [1 ,2 ]
Avezum, Alvaro [11 ,12 ]
Basile, Jan [13 ]
Chung, Namsik [14 ]
Conget, Ignacio [15 ]
Cushman, William C. [16 ]
Franek, Edward [17 ,18 ]
Hancu, Nicolae [19 ]
Hanefeld, Markolf [20 ]
Holt, Shaun [21 ]
Jansky, Petr [22 ]
Keltai, Matyas [23 ]
Lanas, Fernando [24 ]
Leiter, Lawrence A. [25 ]
Lopez-Jaramillo, Patricio [26 ,27 ]
Cardona Munoz, Ernesto German [28 ]
Pirags, Valdis [29 ]
Pogosova, Nana [30 ]
Raubenheimer, Peter J. [31 ]
Shaw, Jonathan E. [32 ]
Sheu, Wayne H-H [33 ]
Temelkova-Kurktschiev, Theodora [34 ]
机构
[1] McMaster Univ, Populat Hlth Res Inst, Hamilton, ON L8S 4K1, Canada
[2] Hamilton Hlth Sci, Hamilton, ON L8S 4K1, Canada
[3] Univ Edinburgh, Edinburgh, Midlothian, Scotland
[4] Univ Laval, Inst Univ Cardiol & Pneumol, Quebec City, PQ, Canada
[5] Estudios Clin Latinoamer, ECLA, Rosario, Santa Fe, Argentina
[6] Eli Lilly & Co, Indianapolis, IN 46285 USA
[7] St Johns Res Inst, Bangalore, Karnataka, India
[8] Univ Washington, Dept Med, Seattle, WA USA
[9] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA
[10] Karolinska Inst, Dept Med K2, Stockholm, Sweden
[11] Inst Dante Pazzanese Cardiol, Sao Paulo, Brazil
[12] Univ Santo Amaro, Sao Paulo, Brazil
[13] Med Univ South Carolina, Charleston, SC 29425 USA
[14] Yonsei Univ Hlth Syst, Seoul, South Korea
[15] Hosp Clin & Univ, Endocrinol & Nutr Dept, Barcelona, Spain
[16] Memphis Vet Affairs Med Ctr, Memphis, TN USA
[17] Polish Acad Sci, Mossakowski Med Res Ctr, Warsaw, Poland
[18] Cent Clin Hosp MSWiA, Warsaw, Poland
[19] Iuliu Hatieganu Univ Med & Pharm, Cluj Napoca, Romania
[20] Tech Univ Dresden, Dept Internal Med, Dresden, Germany
[21] Victoria Univ Wellington, Wellington, New Zealand
[22] Univ Hosp Motol, Prague, Czech Republic
[23] Semmelweis Univ, Hungarian Inst Cardiol, Budapest, Hungary
[24] Univ La Frontera, Temuco, Chile
[25] Univ Toronto, St Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON, Canada
[26] Univ Santander UDES, FOSCAL, Res Inst, Bucaramanga, Colombia
[27] Univ Santander UDES, Med Sch, Bucaramanga, Colombia
[28] Univ Guadalajara, Ctr Univ Ciencias Salud, Guadalajara, Jalisco, Mexico
[29] Latvijas Univ, Riga, Latvia
[30] Natl Med Res Ctr Cardiol, Moscow, Russia
[31] Univ Cape Town, Cape Town, South Africa
[32] Baker Heart & Diabet Inst, Melbourne, Vic, Australia
[33] Taichung Vet Gen Hosp, Taichung, Taiwan
[34] Robert Koch Med Ctr, Sofia, Bulgaria
关键词
PEPTIDE-1 RECEPTOR AGONISTS; BASE-LINE; EFFICACY; EVENTS; SAFETY;
D O I
10.1016/S0140-6736(19)31149-3
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Three different glucagon-like peptide-1 (GLP-1) receptor agonists reduce cardiovascular outcomes in people with type 2 diabetes at high cardiovascular risk with high glycated haemoglobin A 1c (HbA 1c) concentrations. We assessed the effect of the GLP-1 receptor agonist dulaglutide on major adverse cardiovascular events when added to the existing antihyperglycaemic regimens of individuals with type 2 diabetes with and without previous cardiovascular disease and a wide range of glycaemic control. Methods This multicentre, randomised, double-blind, placebo-controlled trial was done at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1: 1) to either weekly subcutaneous injection of dulaglutide (1.5 mg) or placebo. Randomisation was done by a computer-generated random code with stratification by site. All investigators and participants were masked to treatment assignment. Participants were followed up at least every 6 months for incident cardiovascular and other serious clinical outcomes. The primary outcome was the first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes (including unknown causes), which was assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01394952. Findings Between Aug 18, 2011, and Aug 14, 2013, 9901 participants (mean age 66.2 years [SD 6.5], median HbA 1c 7.2% [IQR 6.6-8.1], 4589 [46.3%] women) were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). During a median follow-up of 5.4 years (IQR 5.1-5.9), the primary composite outcome occurred in 594 (12.0%) participants at an incidence rate of 2.4 per 100 person-years in the dulaglutide group and in 663 (13.4%) participants at an incidence rate of 2.7 per 100 person-years in the placebo group (hazard ratio [HR] 0.88, 95% CI 0.79-0.99; p=0.026). All-cause mortality did not differ between groups (536 [10.8%] in the dulaglutide group vs 592 [12.0%] in the placebo group; HR 0.90, 95% CI 0.80-1.01; p=0.067). 2347 (47.4%) participants assigned to dulaglutide reported a gastrointestinal adverse event during follow-up compared with 1687 (34.1%) participants assigned to placebo (p< 0.0001). Interpretation Dulaglutide could be considered for the management of glycaemic control in middle-aged and older people with type 2 diabetes with either previous cardiovascular disease or cardiovascular risk factors. Copyright (c) 2019 Elsevier Ltd. All rights reserved.
引用
收藏
页码:121 / 130
页数:10
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